| Project/Area Number |
18590061
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kumamoto University |
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Principal Investigator |
ISOHAMA Yoichiro Kumamoto University, Graduate School of Pharmaceutical Sciences, Department of Chemico-Pharmacological Sciences, Associate Professor (10240920)
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| Co-Investigator(Kenkyū-buntansha) |
HISATSUNE Akinori Kumamoto University, Graduate School of Pharmaceutical Sciences, Department of Chemico-Pharmacological Sciences, Associate Professor (50347001)
MIYATA Takeshi Sojo University, Faculty of Pharmaceutical Sciences, Laboratory of Presymptomatic Medical Pharmacology, Professor (90040310)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | alveolar epithelial cell / gas exchange / aquaporin / nitric oxide / DNA methylation / CO_2がス透過性 |
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| Research Abstract |
O_2 and CO_2 gas transport through plasma membrane is important to maintain normal respiration between alveolar space and blood flow. We have previously indicated that aquaporins (AQPs) enhances movement of CO_2 gas, as well as water, across plasma membrane, and suggested that the increase in AQP expression might enhance gas exchange at alveoli. In this study, therefore, we first examined the mechanism of AQP5 expression in alveolar epithelial cells. It has been defined that promoter region of AQP5 gene was methylated in the cell types without AQP5, whereas it was demethylated in alveolar type I cells. The methylation of AQP5 DNA significantly decreased its transcriptional activity and the binding to Sp1 transcription factor. We have also found all-trans retinoic acid as a new AQP5 inducer. Retinoic acid increased AQP5 transcription through the activation of Sp1. In addition, we examined the effect of nitric oxide (NO), which is an important inflammatory mediator, on AQP5 activity. NO decreased AQP5 activity by S-nitrosylation of cystein residue in the water pore of AQP5.We finally, prepared CHO cells which stably express AQP5. The growth and morphology were same with those of control CHO cells without AQP5. However, the apoptosis induced by hypoxia was significantly less than that in control cells. Interestingly, glucose deprivation induced apoptosis equally in both cells, suggesting increased gas metabolism by AQP5 might inhibit hypoxia-induced apoptosis in AQP5-expressing cells. These findings are useful to consider the new strategies to enhance gas exchange at alveolar-blood barrier in various respiratory diseases.
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